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Tislelizumab Combined With IMRT Neoadjuvant Treatment for Resectable Hepatocellular Carcinoma With PVTT

Primary Purpose

Hepatocellular Carcinoma With Portal Vein Tumor Thrombus

Status
Not yet recruiting
Phase
Phase 2
Locations
China
Study Type
Interventional
Intervention
Tislelizumab
IMRT
Sponsored by
Shanghai Zhongshan Hospital
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Hepatocellular Carcinoma With Portal Vein Tumor Thrombus

Eligibility Criteria

18 Years - 75 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • Histologically or cytologically confirmed hepatocellular carcinoma
  • Patients with at least one measurable lesion
  • Resectable primary lesion, PVTTⅡ-Ⅲtype
  • No previous treatment for hepatocellular carcinoma
  • Eastern Cooperative Oncology Group(ECOG): Performance Status(PS)score 0-1
  • Child-Pugh score A
  • Expected survival ≥ 3 months
  • Baseline blood routine and blood biochemical indicators should meet the following criteria:

hemoglobin ≥ 90 g/L, absolute neutrophil count ≥ 1.5 × 10 ^/L, platelet count ≥ 75 × 10 ^/L aspartate or alanine aminotransferase 5 times the upper limit of normal (ULN), alkaline phosphatase ≤ 2.5 times the ULN, serum albumin ≥ 30 g/L; serum creatinine 1.5 times the ULN; international normalized ratio (INR)) ≤ 2 or prothrombin time (PT) more than the upper limit of normal range ≤ 6 seconds

  • Appropriate to participate in this trial as assessed by the investigator before entering the study
  • Male and female subjects of childbearing potential must agree to use an effective method of contraception throughout the study
  • Signed informed consent.

Exclusion Criteria:

  • Imaging showed distant metastasis
  • Previous treatment with other effective regimens (including surgery, radiotherapy, systemic therapy, etc.)
  • Previous allergic reactions to the same kind of drugs
  • Pregnant or lactating patients
  • Active hepatitis B or C (hepatitis B: HBsAg positive and Hepatitis B (HBV )DNA ≥ 1*10^4 IU/ml; hepatitis C: hepatitis C virus (HCV) antibody and HCV RNA positive, requiring simultaneous antiviral therapy)
  • Pericardial effusion, uncontrolled pleural effusion or clinically severe ascites at screening
  • History of interstitial lung disease, pneumonitis, or uncontrolled systemic disease, including diabetes, hypertension, pulmonary fibrosis, acute lung disease
  • Suffering from severe cardiovascular disease within 12 months before screening, such as symptomatic coronary heart disease,≥II congestive heart failure, uncontrolled arrhythmia, infarction, etc
  • Any active immunodeficiency or autoimmune disease at screening and/or any history of immunodeficiency or autoimmune disease that may recur (such as hypothyroidism or hyperthyroidism, interstitial pneumonia, enteritis, hepatitis, hypophysitis, vasculitis, myocarditis, etc.)
  • Use of steroids or other systemic immunosuppressive therapy 14 days before enrollment; use of steroids or other systemic immunosuppressive therapy
  • Patients with other previous malignancies that are not cured; Patients with other previous malignancies that are not cured
  • Immunocompromised patients, such as immunocompromised patients, such as human immunodeficiency virus (HIV) positive; positive
  • With uncontrollable psychosis; With uncontrollable psychosis
  • Other factors make the investigators think it is inappropriate to participate in this trial.

Sites / Locations

  • Zhongshan hospital, Fudan University

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Tislelizumab+IMRT

Arm Description

Outcomes

Primary Outcome Measures

Relapse-free survival( RFS)
Defined as the time from the date of surgery to the date of disease recurrence or death whichever occur first

Secondary Outcome Measures

Resection rate (R0 resection rate)
Defined as the proportion of patients undergoing radical resection to the total subjects (R0 resection rate)
Objective response rate (ORR) assessed by mRECIST
Defined as the proportion of patients who had a best overall tumor response rating of complete response (CR) or partial response (PR).
Overall survival (OS)
Defined as the time from the date of treatment start to the date of death or to the date of last follow-up for patients alive
Adverse Events (AEs)
Defined as the proportion of patients with AE, treatment-related AE (TRAE), immune-related AE (irAE), serious adverse event (SAE), assessed by NCI CTCAE v5.0; Surgical safety including Intraoperative blood loss，PHLF assessed by ISGLS（2012），Postoperative complications evaluated by modified Clavien-Dindo system.

Full Information

First Posted
April 12, 2021
Last Updated
April 19, 2021
Sponsor
Shanghai Zhongshan Hospital
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1. Study Identification

Unique Protocol Identification Number
NCT04850157
Brief Title
Tislelizumab Combined With IMRT Neoadjuvant Treatment for Resectable Hepatocellular Carcinoma With PVTT
Official Title
Tislelizumab Combined With Intensity Modulated Radiation Therapy（IMRT) Neoadjuvant Treatment for Resectable Hepatocellular Carcinoma With Portal Vein Tumor Thrombus
Study Type
Interventional

2. Study Status

Record Verification Date
April 2021
Overall Recruitment Status
Not yet recruiting
Study Start Date
April 20, 2021 (Anticipated)
Primary Completion Date
April 20, 2022 (Anticipated)
Study Completion Date
December 20, 2023 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Shanghai Zhongshan Hospital

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

Brief Summary
Due to the biological characteristics and liver anatomical characteristics of liver cancer, liver cancer cells easily invade the vascular system, especially the portal venous system, forming portal vein tumor thrombus (PVTT) , and its incidence is reported to be 44.0% ~ 62.2%. Once PVTT occurs in patients with liver cancer, the disease develops rapidly, and intrahepatic and extrahepatic metastasis, portal hypertension, jaundice, and abdominal effusion can occur in a short time with an average survival time of 2.7 months. PVTT is one of the major adverse factors for the prognosis of liver cancer and occupies an important weight influence in the clinical staging system of liver cancer. In some hepatocellular carcinoma (HCC) patients with PVTT and selective resectability, surgery versus non-surgery can lead to better survival of patients. A retrospective analysis showed that neoadjuvant radiotherapy can reduce the extent of invasion of PVTT and improve postoperative survival in some HCC patients. Another prospective study showed that neoadjuvant radiotherapy could significantly improve the overall survival of resectable liver cancer with PVTT, and neoadjuvant radiotherapy could improve the 2-year survival of patients from 9.4% to 27.4% 27.4%, with an effective response of 20.7%. This study is a prospective, single-center, single-arm study to assess the efficacy and safety of neoadjuvant therapy with tislelizumab combined with IMRT for resectable liver cancer with PVTT.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Hepatocellular Carcinoma With Portal Vein Tumor Thrombus

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
30 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Tislelizumab+IMRT
Arm Type
Experimental
Intervention Type
Drug
Intervention Name(s)
Tislelizumab
Intervention Description
200mg, Q3W
Intervention Type
Radiation
Intervention Name(s)
IMRT
Intervention Description
4 Gy* 5 Fx,5Fx/Week
Primary Outcome Measure Information:
Title
Relapse-free survival( RFS)
Description
Defined as the time from the date of surgery to the date of disease recurrence or death whichever occur first
Time Frame
Up to 2 years
Secondary Outcome Measure Information:
Title
Resection rate (R0 resection rate)
Description
Defined as the proportion of patients undergoing radical resection to the total subjects (R0 resection rate)
Time Frame
Up to 2 years
Title
Objective response rate (ORR) assessed by mRECIST
Description
Defined as the proportion of patients who had a best overall tumor response rating of complete response (CR) or partial response (PR).
Time Frame
Up to 2 years
Title
Overall survival (OS)
Description
Defined as the time from the date of treatment start to the date of death or to the date of last follow-up for patients alive
Time Frame
Up to 2 years
Title
Adverse Events (AEs)
Description
Defined as the proportion of patients with AE, treatment-related AE (TRAE), immune-related AE (irAE), serious adverse event (SAE), assessed by NCI CTCAE v5.0; Surgical safety including Intraoperative blood loss，PHLF assessed by ISGLS（2012），Postoperative complications evaluated by modified Clavien-Dindo system.
Time Frame
Up to 2 years

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
75 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Histologically or cytologically confirmed hepatocellular carcinoma Patients with at least one measurable lesion Resectable primary lesion, PVTTⅡ-Ⅲtype No previous treatment for hepatocellular carcinoma Eastern Cooperative Oncology Group(ECOG): Performance Status(PS)score 0-1 Child-Pugh score A Expected survival ≥ 3 months Baseline blood routine and blood biochemical indicators should meet the following criteria: hemoglobin ≥ 90 g/L, absolute neutrophil count ≥ 1.5 × 10 ^/L, platelet count ≥ 75 × 10 ^/L aspartate or alanine aminotransferase 5 times the upper limit of normal (ULN), alkaline phosphatase ≤ 2.5 times the ULN, serum albumin ≥ 30 g/L; serum creatinine 1.5 times the ULN; international normalized ratio (INR)) ≤ 2 or prothrombin time (PT) more than the upper limit of normal range ≤ 6 seconds Appropriate to participate in this trial as assessed by the investigator before entering the study Male and female subjects of childbearing potential must agree to use an effective method of contraception throughout the study Signed informed consent. Exclusion Criteria: Imaging showed distant metastasis Previous treatment with other effective regimens (including surgery, radiotherapy, systemic therapy, etc.) Previous allergic reactions to the same kind of drugs Pregnant or lactating patients Active hepatitis B or C (hepatitis B: HBsAg positive and Hepatitis B (HBV )DNA ≥ 1*10^4 IU/ml; hepatitis C: hepatitis C virus (HCV) antibody and HCV RNA positive, requiring simultaneous antiviral therapy) Pericardial effusion, uncontrolled pleural effusion or clinically severe ascites at screening History of interstitial lung disease, pneumonitis, or uncontrolled systemic disease, including diabetes, hypertension, pulmonary fibrosis, acute lung disease Suffering from severe cardiovascular disease within 12 months before screening, such as symptomatic coronary heart disease,≥II congestive heart failure, uncontrolled arrhythmia, infarction, etc Any active immunodeficiency or autoimmune disease at screening and/or any history of immunodeficiency or autoimmune disease that may recur (such as hypothyroidism or hyperthyroidism, interstitial pneumonia, enteritis, hepatitis, hypophysitis, vasculitis, myocarditis, etc.) Use of steroids or other systemic immunosuppressive therapy 14 days before enrollment; use of steroids or other systemic immunosuppressive therapy Patients with other previous malignancies that are not cured; Patients with other previous malignancies that are not cured Immunocompromised patients, such as immunocompromised patients, such as human immunodeficiency virus (HIV) positive; positive With uncontrollable psychosis; With uncontrollable psychosis Other factors make the investigators think it is inappropriate to participate in this trial.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Xinrong Yang
Phone
86-13764295279
Email
yang.xinrong@zs-hospital.sh.cn
Facility Information:
Facility Name
Zhongshan hospital, Fudan University
City
Shanghai
Country
China
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Xinrong Yang
Email
yang.xinrong@zs-hospital.sh.cn
First Name & Middle Initial & Last Name & Degree
Jian Zhou

12. IPD Sharing Statement

Plan to Share IPD
Undecided

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Tislelizumab Combined With IMRT Neoadjuvant Treatment for Resectable Hepatocellular Carcinoma With PVTT

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